Hyperactivation of oxidative mitochondrial metabolism in epithelial cancer cells in situ

References

• Whitaker-Menezes D, Martinez-Outschoorn UE, Lin Z, Ertel A, Flomenberg N, Witkiewicz AK, et al. Evidence for a stromal-epithelial “lactate shuttle” in human tumors: MCT4 is a marker of oxidative stress in cancer-associated fibroblasts. Cell Cycle 2011; 10:1772 - 1783; PMID: 21558814; http://dx.doi.org/10.4161/cc.10.11.15659
   PubMed Web of Science ®Google Scholar
• Sotgia F, Martinez-Outschoorn UE, Pavlides S, Howell A, Pestell RG, Lisanti MP. Understanding the Warburg effect and the prognostic value of stromal caveolin-1 as a marker of a lethal tumor microenvironment. Breast Cancer Res 2011; 13:213; PMID: 21867571; http://dx.doi.org/10.1186/bcr2892
   PubMed Web of Science ®Google Scholar
• Martinez-Outschoorn UE, Pavlides S, Howell A, Pestell RG, Tanowitz HB, Sotgia F, et al. Stromalepithelial metabolic coupling in cancer: integrating autophagy and metabolism in the tumor microenvironment. Int J Biochem Cell Biol 2011; 43:1045 - 1051; PMID: 21300172; http://dx.doi.org/10.1016/j.biocel.2011.01.023
   PubMed Web of Science ®Google Scholar
• Pavlides S, Vera I, Gandara R, Sneddon S, Pestell R, Mercier I, et al. Warburg Meets Autophagy: Cancer Associated Fibroblasts Accelerate Tumor Growth and Metastasis Via Oxidative Stress, Mitophagy and Aerobic Glycolysis. Antioxid Redox Signal 2011; In press PMID: 21883043; http://dx.doi.org/10.1089/ars.2011.4243
   PubMed Web of Science ®Google Scholar
• Brooks GA. Current concepts in lactate exchange. Med Sci Sports Exerc 1991; 23:895 - 906; PMID: 1956262; http://dx.doi.org/10.1249/00005768-199108000-00003
   PubMed Web of Science ®Google Scholar
• Brooks GA. Lactate shuttles in nature. Biochem Soc Trans 2002; 30:258 - 264; PMID: 12023861; http://dx.doi.org/10.1042/BST0300258
   PubMed Web of Science ®Google Scholar
• Brooks GA. Lactate: link between glycolytic and oxidative metabolism. Sports Med 2007; 37:341 - 343; PMID: 17465603; http://dx.doi.org/10.2165/00007256200737040-00017
   PubMed Web of Science ®Google Scholar
• Gladden LB. A lactatic perspective on metabolism. Med Sci Sports Exerc 2008; 40:477 - 485; PMID: 18379210; http://dx.doi.org/10.1249/MSS.0b013e31815fa580
   PubMed Web of Science ®Google Scholar
• Tritschler HJ, Bonilla E, Lombes A, Andreetta F, Servidei S, Schneyder B, et al. Differential diagnosis of fatal and benign cytochrome c oxidase-deficient myopathies of infancy: an immunohistochemical approach. Neurology 1991; 41:300 - 305; PMID: 1846953
   PubMed Web of Science ®Google Scholar
• Lombes A, Nakase H, Tritschler HJ, Kadenbach B, Bonilla E, DeVivo DC, et al. Biochemical and molecular analysis of cytochrome c oxidase deficiency in Leigh's syndrome. Neurology 1991; 41:491 - 498; PMID: 1849240
   PubMed Web of Science ®Google Scholar
• DiMauro S, Lombes A, Nakase H, Mita S, Fabrizi GM, Tritschler HJ, et al. Cytochrome c oxidase deficiency. Pediatr Res 1990; 28:536 - 541; PMID: 2175026; http://dx.doi.org/10.1203/00006450-199011000-00025
   PubMed Web of Science ®Google Scholar
• DiMauro S. Pathogenesis and treatment of mitochondrial myopathies: recent advances. Acta Myol 2010; 29:333 - 338; PMID: 21314015
   PubMedGoogle Scholar
• DiMauro S, Garone C. Historical perspective on mitochondrial medicine. Dev Disabil Res Rev 2010; 16:106 - 113; PMID: 20818724; http://dx.doi.org/10.1002/ddrr.102
   PubMed Web of Science ®Google Scholar
• DiMauro S, Garone C, Naini A. Metabolic myopathies. Curr Rheumatol Rep 2010; 12:386 - 393; PMID: 20676808; http://dx.doi.org/10.1007/s11926-010-0119-9
   PubMedGoogle Scholar
• DiMauro S, Hirano M. Pathogenesis and treatment of mitochondrial disorders. Adv Exp Med Biol 2009; 652:139 - 170; PMID: 20225024; http://dx.doi.org/10.1007/978-90481-2813-6_10
   PubMed Web of Science ®Google Scholar
• Dimauro S, Rustin P. A critical approach to the therapy of mitochondrial respiratory chain and oxidative phosphorylation diseases. Biochim Biophys Acta 2009; 1792:1159 - 1167; PMID: 19026744
   PubMed Web of Science ®Google Scholar
• Seligman AM, Karnovsky MJ, Wasserkrug HL, Hanker JS. Nondroplet ultrastructural demonstration of cytochrome oxidase activity with a polymerizing osmiophilic reagent, diaminobenzidine (DAB). J Cell Biol 1968; 38:1 - 14; PMID: 4300067; http://dx.doi.org/10.1083/jcb.38.1.1
   PubMed Web of Science ®Google Scholar
• Pavlides S, Whitaker-Menezes D, Castello-Cros R, Flomenberg N, Witkiewicz AK, Frank PG, et al. The reverse Warburg effect: Aerobic glycolysis in cancer associated fibroblasts and the tumor stroma. Cell Cycle 2009; 8:3984 - 4001; PMID: 19923890; http://dx.doi.org/10.4161/cc.8.23.10238
   PubMed Web of Science ®Google Scholar
• Pavlides S, Tsirigos A, Migneco G, Whitaker-Menezes D, Chiavarina B, Flomenberg N, et al. The Autophagic Tumor Stroma Model of Cancer: Role of Oxidative Stress and Ketone Production in Fueling Tumor Cell Metabolism. Cell Cycle 2010; 9:3485 - 3505; PMID: 20861672; http://dx.doi.org/10.4161/cc.9.17.12721
   PubMed Web of Science ®Google Scholar
• Martinez-Outschoorn UE, Pavlides S, Whitaker-Menezes D, Daumer KM, Milliman JN, Chiavarina B, et al. Tumor Cells Induce the Cancer Associated Fibroblast Phenotype Via Caveolin-1 Degradation: Implications for Breast Cancer and DCIS Therapy with Autophagy Inhibitors. Cell Cycle 2010; 9:2423 - 2433; PMID: 20562526; http://dx.doi.org/10.4161/cc.9.12.12048
   PubMed Web of Science ®Google Scholar
• Martinez-Outschoorn UE, Balliet RM, Rivadeneira DB, Chiavarina B, Pavlides S, Wang C, et al. Oxidative Stress in Cancer Associated Fibroblasts Drives Tumor-Stroma Co-Evolution: A New Paradigm for Understanding Tumor Metabolism, the Field Effect and Genomic Instability in Cancer Cells. Cell Cycle 2010; 9:3256 - 3276; PMID: 20814239; http://dx.doi.org/10.4161/cc.9.16.12553
   PubMed Web of Science ®Google Scholar
• Martinez-Outschoorn UE, Trimmer C, Lin Z, Whitaker-Menezes D, Chiavarina B, Zhou J, et al. Autophagy in Cancer Associated Fibroblasts Promotes Tumor Cell Survival: Role of Hypoxia, HIF1 Induction and NFκB Activation in the Tumor Stromal Microenvironment. Cell Cycle 2010; 9:3515 - 3533; PMID: 20855962; http://dx.doi.org/10.4161/cc.9.17.12928
   PubMed Web of Science ®Google Scholar
• Chiavarina B, Whitaker-Menezes D, Migneco G, Martinez-Outschoorn UE, Pavlides S, Howell A, et al. HIF-1alpha Functions as a Tumor Promoter in Cancer Associated Fibroblasts, and as a Tumor Suppressor in Breast Cancer Cells: Autophagy Drives Compartment-Specific Oncogenesis. Cell Cycle 2010; 9:3534 - 3551; PMID: 20864819; http://dx.doi.org/10.4161/cc.9.17.12908
   PubMed Web of Science ®Google Scholar
• Trimmer C, Sotgia F, Whitaker-Menezes D, Balliet RM, Eaton G, Martinez-Outschoorn UE, et al. Caveolin-1 and mitochondrial SOD2 (MnSOD) function as tumor suppressors in the stromal microenvironment: a new genetically tractable model for human cancer associated fibroblasts. Cancer Biol Ther 2011; 11:383 - 394; PMID: 21150282; http://dx.doi.org/10.4161/cbt.11.4.14101
   PubMed Web of Science ®Google Scholar
• Brunmair B, Staniek K, Gras F, Scharf N, Althaym A, Clara R, et al. Thiazolidinediones, like metformin, inhibit respiratory complex I: a common mechanism contributing to their antidiabetic actions?. Diabetes 2004; 53:1052 - 1059; PMID: 15047621; http://dx.doi.org/10.2337/diabetes.53.4.1052
   PubMed Web of Science ®Google Scholar
• Detaille D, Guigas B, Leverve X, Wiernsperger N, Devos P. Obligatory role of membrane events in the regulatory effect of metformin on the respiratory chain function. Biochem Pharmacol 2002; 63:1259 - 1272; PMID: 11960602; http://dx.doi.org/10.1016/S00062952(02)00858-4
   PubMed Web of Science ®Google Scholar
• El-Mir MY, Nogueira V, Fontaine E, Averet N, Rigoulet M, Leverve X. Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I. J Biol Chem 2000; 275:223 - 228; PMID: 10617608; http://dx.doi.org/10.1074/jbc.275.1.223
   PubMed Web of Science ®Google Scholar
• Owen MR, Doran E, Halestrap AP. Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem J 2000; 348:607 - 614; PMID: 10839993; http://dx.doi.org/10.1042/0264-6021:3480607
   PubMed Web of Science ®Google Scholar
• Biradar V, Moran JL, Peake SL, Peter JV. Metforminassociated lactic acidosis (MALA): clinical profile and outcomes in patients admitted to the intensive care unit. Crit Care Resusc 2010; 12:191 - 195; PMID: 21261578
   PubMed Web of Science ®Google Scholar
• Dykens JA, Jamieson J, Marroquin L, Nadanaciva S, Billis PA, Will Y. Biguanide-induced mitochondrial dysfunction yields increased lactate production and cytotoxicity of aerobically-poised HepG2 cells and human hepatocytes in vitro. Toxicol Appl Pharmacol 2008; 233:203 - 210; PMID: 18817800; http://dx.doi.org/10.1016/j.taap.2008.08.013
   PubMed Web of Science ®Google Scholar
• Hirsch HA, Iliopoulos D, Tsichlis PN, Struhl K. Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission. Cancer Res 2009; 69:7507 - 7511; PMID: 19752085; http://dx.doi.org/10.1158/0008-5472.CAN09-2994
   PubMed Web of Science ®Google Scholar
• Memmott RM, Mercado JR, Maier CR, Kawabata S, Fox SD, Dennis PA. Metformi prevents tobacco carcinogen-induced lung tumorigenesis. Cancer Prev Res (Phila) 2010; 3:1066 - 1076; PMID: 20810672; http://dx.doi.org/10.1158/1940-6207.CAPR-10-0055
   PubMed Web of Science ®Google Scholar
• Pollak M. Metformin and other biguanides in oncology: advancing the research agenda. Cancer Prev Res (Phila) 2010; 3:1060 - 1065; PMID: 20810670; http://dx.doi.org/10.1158/1940-6207.CAPR-10-0175
   PubMed Web of Science ®Google Scholar
• Vazquez-Martin A, Oliveras-Ferraros C, Barco SD, Martin-Castillo B, Menendez JA. The anti-diabetic drug metformin suppresses self-renewal and proliferation of trastuzumab-resistant tumor-initiating breast cancer stem cells. Breast Cancer Res Treat 2011; 126:355 - 364; PMID: 20458531; http://dx.doi.org/10.1007/s10549010-0924-x
   PubMed Web of Science ®Google Scholar
• Vazquez-Martin A, Oliveras-Ferraros C, Cufi S, Del Barco S, Martin-Castillo B, Menendez JA. Metformin regulates breast cancer stem cell ontogeny by transcriptional regulation of the epithelial-mesenchymal transition (EMT) status. Cell Cycle 2010; 9:3807 - 3814; PMID: 20890129; http://dx.doi.org/10.4161/cc.9.18.13131
   PubMed Web of Science ®Google Scholar
• Vazquez-Martin A, Oliveras-Ferraros C, Cufi S, Martin-Castillo B, Menendez JA. Metformin and energy metabolism in breast cancer: from insulin physiology to tumour-initiating stem cells. Curr Mol Med 2010; 10:674 - 691; PMID: 20712585; http://dx.doi.org/10.2174/156652410792630625
   PubMed Web of Science ®Google Scholar
• Pavlides S, Tsirigos A, Vera I, Flomenberg N, Frank PG, Casimiro MC, et al. Transcriptional evidence for the “Reverse Warburg Effect” in human breast cancer tumor stroma and metastasis: similarities with oxidative stress, inflammation, Alzheimer's disease and “Neuron-Glia Metabolic Coupling”. Aging (Albany NY) 2010; 2:185 - 199; PMID: 20442453
   PubMedGoogle Scholar
• Pavlides S, Tsirigos A, Vera I, Flomenberg N, Frank PG, Casimiro MC, et al. Loss of Stromal Caveolin-1 Leads to Oxidative Stress, Mimics Hypoxia and Drives Inflammation in the Tumor Microenvironment, Conferring the “Reverse Warburg Effect”: A Transcriptional Informatics Analysis with Validation. Cell Cycle 2010; 9:2201 - 2219; PMID: 20519932; http://dx.doi.org/10.4161/cc.9.11.11848
   PubMed Web of Science ®Google Scholar
• Martinez-Outschoorn UE, Whitaker-Menezes D, Pavlides S, Chiavarina B, Bonuccelli G, Casey T, et al. The Autophagic Tumor Stroma Model of Cancer or “Battery-Operated Tumor Growth”: A Simple Solution to the Autophagy Paradox. Cell Cycle 2010; 9:4297 - 4306; PMID: 21051947; http://dx.doi.org/10.4161/cc.9.21.13817
   PubMed Web of Science ®Google Scholar
• Clark JB, Hayes DJ, Morgan-Hughes JA, Byrne E. Mitochondrial myopathies: disorders of the respiratory chain and oxidative phosphorylation. J Inherit Metab Dis 1984; 7:62 - 68; PMID: 6434847; http://dx.doi.org/10.1007/BF03047377
   PubMed Web of Science ®Google Scholar
• Sengers RC, Stadhouders AM, Trijbels JM. Mitochondrial myopathies. Clinical, morphological and biochemical aspects. Eur J Pediatr 1984; 141:192 - 207; PMID: 6329761; http://dx.doi.org/10.1007/BF00572761
   PubMed Web of Science ®Google Scholar
• Leverve XM, Guigas B, Detaille D, Batandier C, Koceir EA, Chauvin C, et al. Mitochondrial metabolism and type-2 diabetes: a specific target of metformin. Diabetes Metab 2003; 29:88 - 94; PMID: 14502105; http://dx.doi.org/10.1016/S1262-3636(03)72792-X
   PubMedGoogle Scholar
• Batandier C, Guigas B, Detaille D, El-Mir MY, Fontaine E, Rigoulet M, et al. The ROS production induced by a reverse-electron flux at respiratory-chain complex 1 is hampered by metformin. J Bioenerg Biomembr 2006; 38:33 - 42; PMID: 16732470; http://dx.doi.org/10.1007/s10863-006-9003-8
   PubMed Web of Science ®Google Scholar
• Bonuccelli G, Tsirigos A, Whitaker-Menezes D, Pavlides S, Pestell RG, Chiavarina B, et al. Ketones and Lactate “Fuel” Tumor Growth and Metastasis: Evidence that Epithelial Cancer Cells Use Oxidative Mitochondrial Metabolism. Cell Cycle 2010; 9:3506 - 3514; PMID: 20818174; http://dx.doi.org/10.4161/cc.9.17.12731
   PubMed Web of Science ®Google Scholar
• Casey T, Bond J, Tighe S, Hunter T, Lintault L, Patel O, et al. Molecular signatures suggest a major role for stromal cells in development of invasive breast cancer. Breast Cancer Res Treat 2009; 114:47 - 62; PMID: 18373191; http://dx.doi.org/10.1007/s10549-008-9982-8
   PubMed Web of Science ®Google Scholar
• Berridge MV, Tan AS. Effects of mitochondrial gene deletion on tumorigenicity of metastatic melanoma: reassessing the Warburg effect. Rejuvenation Res 2010; 13:139 - 141; PMID: 20370492; http://dx.doi.org/10.1089/rej.2009.0948
   PubMed Web of Science ®Google Scholar
• Koppenol WH, Bounds PL, Dang CV. Otto Warburg's contributions to current concepts of cancer metabolism. Nat Rev Cancer 2011; 11:325 - 337; PMID: 21508971; http://dx.doi.org/10.1038/nrc3038
   PubMed Web of Science ®Google Scholar
• Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 2009; 324:1029 - 1033; PMID: 19460998; http://dx.doi.org/10.1126/science.1160809
   PubMed Web of Science ®Google Scholar
• Kaelin W Jr, Thompson CB. Q&A: Cancer: clues from cell metabolism. Nature 2010; 465:562 - 564; PMID: 20520704; http://dx.doi.org/10.1038/465562a
   PubMed Web of Science ®Google Scholar
• Levine AJ, Puzio-Kuter AM. The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes. Science 2010; 330:1340 - 1344; PMID: 21127244; http://dx.doi.org/10.1126/science.1193494
   PubMed Web of Science ®Google Scholar
• Migneco G, Whitaker-Menezes D, Chiavarina B, Castello-Cros R, Pavlides S, Pestell RG, et al. Glycolytic cancer associated fibroblasts promote breast cancer tumor growth, without a measurable increase in angiogenesis: Evidence for stromal-epithelial metabolic coupling. Cell Cycle 2010; 9:2412 - 2422; PMID: 20562527; http://dx.doi.org/10.4161/cc.9.12.11989
   PubMed Web of Science ®Google Scholar
• Martinez-Outschoorn UE, Prisco M, Ertel A, Tsirigos A, Lin Z, Pavlides S, et al. Ketones and lactate increase cancer cell “stemness,” driving recurrence, metastasis and poor clinical outcome in breast cancer: achieving personalized medicine via Metabolo-Genomics. Cell Cycle 2011; 10:1271 - 1286; PMID: 21512313; http://dx.doi.org/10.4161/cc.10.8.15330
   PubMed Web of Science ®Google Scholar
• Martinez-Outschoorn UE, Goldberg AF, Lin Z, Ko YH, Flomenberg N, Wang C, et al. Anti-estrogen resistance in breast cancer is induced by the tumor microenvironment and can be overcome by inhibiting mitochondrial function in epithelial cancer cells. Cancer Biol Ther 2011; 12:924 - 938
   PubMed Web of Science ®Google Scholar
• Reich NC. STAT3 revs up the powerhouse. Sci Signal 2009; 2:61; PMID: 19797267; http://dx.doi.org/10.1126/scisignal.290pe61
   PubMed Web of Science ®Google Scholar
• Gough DJ, Corlett A, Schlessinger K, Wegrzyn J, Larner AC, Levy DE. Mitochondrial STAT3 supports Ras-dependent oncogenic transformation. Science 2009; 324:1713 - 1716; PMID: 19556508; http://dx.doi.org/10.1126/science.1171721
   PubMed Web of Science ®Google Scholar
• Wegrzyn J, Potla R, Chwae YJ, Sepuri NB, Zhang Q, Koeck T, et al. Function of mitochondrial Stat3 in cellular respiration. Science 2009; 323:793 - 797; PMID: 19131594; http://dx.doi.org/10.1126/science.1164551
   PubMed Web of Science ®Google Scholar
• Spees JL, Olson SD, Whitney MJ, Prockop DJ. Mitochondrial transfer between cells can rescue aerobic respiration. Proc Natl Acad Sci USA 2006; 103:1283 - 1288; PMID: 16432190; http://dx.doi.org/10.1073/pnas.0510511103
   PubMed Web of Science ®Google Scholar
• Rebbeck CA, Leroi AM, Burt A. Mitochondrial capture by a transmissible cancer. Science 2011; 331:303; PMID: 21252340; http://dx.doi.org/10.1126/science.1197696
   PubMed Web of Science ®Google Scholar
• Villanueva T. Metabolism: the mitochondria that wag the dog. Nat Rev Cancer 2011; 11:155; PMID: 21451550; http://dx.doi.org/10.1038/nrc3026
   PubMed Web of Science ®Google Scholar
• Berridge MV, Tan AS. Mitochondrial Gene Transfer to Transplantable Tumours Lacking a Mitochondrial Genome. Rejuvenation Res 2011; 14:13 - 14
   Google Scholar
• Chen EI, Hewel J, Krueger JS, Tiraby C, Weber MR, Kralli A, et al. Adaptation of energy metabolism in breast cancer brain metastases. Cancer Res 2007; 67:1472 - 1486; PMID: 17308085; http://dx.doi.org/10.1158/00085472.CAN-06-3137
   PubMed Web of Science ®Google Scholar
• Wyss MT, Jolivet R, Buck A, Magistretti PJ, Weber B. In vivo evidence for lactate as a neuronal energy source. J Neurosci 2011; 31:7477 - 7485; PMID: 21593331; http://dx.doi.org/10.1523/JNEUROSCI.0415-11.2011
   PubMed Web of Science ®Google Scholar
• Tsuda H, Seki K, Hasebe T, Sasajima Y, Shibata T, Iwamoto E, et al. A histopathological study for evaluation of therapeutic effects of radiofrequency ablation in patients with breast cancer. Breast Cancer 2011; 18:24 - 32; PMID: 20862572; http://dx.doi.org/10.1007/s12282010-0222-9
   PubMed Web of Science ®Google Scholar
• Rohlena J, Dong LF, Ralph SJ, Neuzil J. Anticancer Drugs Targeting the Mitochondrial Electron Transport Chain. Antioxid Redox Signal 2011; 15:2951 - 2974; PMID: 21777145; http://dx.doi.org/10.1089/ars.2011.3990
   PubMed Web of Science ®Google Scholar
• Siegelin MD, Dohi T, Raskett CM, Orlowski GM, Powers CM, Gilbert CA, et al. Exploiting the mitochondrial unfolded protein response for cancer therapy in mice and human cells. J Clin Invest 2011; 121:1349 - 1360; PMID: 21364280; http://dx.doi.org/10.1172/JCI44855
   PubMed Web of Science ®Google Scholar
• Fulda S, Galluzzi L, Kroemer G. Targeting mitochondria for cancer therapy. Nat Rev Drug Discov 2010; 9:447 - 464; PMID: 20467424; http://dx.doi.org/10.1038/nrd3137
   PubMed Web of Science ®Google Scholar
• Kousparou CA, Epenetos AA, Deonarain MP. Antibody-guided enzyme therapy of cancer producing cyanide results in necrosis of targeted cells. Int J Cancer 2002; 99:138 - 148; PMID: 11948505; http://dx.doi.org/10.1002/ijc.10266
   PubMed Web of Science ®Google Scholar
• Gargini R, Garcia-Escudero V, Izquierdo M. Therapy mediated by mitophagy abrogates tumor progression. Autophagy 2011; 7:466 - 476; PMID: 21270513; http://dx.doi.org/10.4161/auto.7.5.14731
   PubMed Web of Science ®Google Scholar
• García-Escudero V, Gargini R. Autophagy induction as an efficient strategy to eradicate tumors. Autophagy 2008; 4:923 - 925; PMID: 18716458
   PubMed Web of Science ®Google Scholar
• Gallagher SM, Castorino JJ, Wang D, Philp NJ. Monocarboxylate transporter 4 regulates maturation and trafficking of CD147 to the plasma membrane in the metastatic breast cancer cell line MDA-MB-231. Cancer Res 2007; 67:4182 - 4189; PMID: 17483329; http://dx.doi.org/10.1158/0008-5472.CAN-06-3184
   PubMed Web of Science ®Google Scholar
• Witkiewicz AK, Kline J, Queenan M, Brody JR, Tsirigos A, Bilal E, et al. Molecular profiling of a lethal tumor microenvironment, as defined by stromal caveolin-1 status in breast cancers. Cell Cycle 2011; 10:1794 - 1809; PMID: 21521946; http://dx.doi.org/10.4161/cc.10.11.15675
   PubMed Web of Science ®Google Scholar
• Witkiewicz AK, Dasgupta A, Sotgia F, Mercier I, Pestell RG, Sabel M, et al. An Absence of Stromal Caveolin-1 Expression Predicts Early Tumor Recurrence and Poor Clinical Outcome in Human Breast Cancers. Am J Pathol 2009; 174:2023 - 2034; PMID: 19411448; http://dx.doi.org/10.2353/ajpath.2009.080873
   PubMed Web of Science ®Google Scholar
• Witkiewicz AK, Dasgupta A, Nguyen KH, Liu C, Kovatich AJ, Schwartz GF, et al. Stromal caveolin-1 levels predict early DCIS progression to invasive breast cancer. Cancer Biol Ther 2009; 8:1071 - 1079; PMID: 19502809; http://dx.doi.org/10.4161/cbt.8.11.8874
   PubMed Web of Science ®Google Scholar
• Witkiewicz AK, Dasgupta A, Sammons S, Er O, Potoczek MB, Guiles F, et al. Loss of Stromal Caveolin-1 Expression Predicts Poor Clinical Outcome in Triple Negative and Basal-like Breast Cancers. Cancer Biol Ther 2010; 10:135 - 143; PMID: 20431349; http://dx.doi.org/10.4161/cbt.10.2.11983
   PubMed Web of Science ®Google Scholar
• Witkiewicz AK, Casimiro MC, Dasgupta A, Mercier I, Wang C, Bonuccelli G, et al. Towards a new “stromalbased” classification system for human breast cancer prognosis and therapy. Cell Cycle 2009; 8:1654 - 1658; PMID: 19448435; http://dx.doi.org/10.4161/cc.8.11.8544
   PubMed Web of Science ®Google Scholar
• Ghajar CM, Meier R, Bissell MJ. Quis custodiet ipsos custodies: who watches the watchmen?. Am J Pathol 2009; 174:1996 - 1999; PMID: 19465642; http://dx.doi.org/10.2353/ajpath.2009.090363
   PubMed Web of Science ®Google Scholar
• Sloan EK, Ciocca D, Pouliot N, Natoli A, Restall C, Henderson M, et al. Stromal Cell Expression of Caveolin-1 Predicts Outcome in Breast Cancer. Am J Pathol 2009; 174:2035 - 2043; PMID: 19411449; http://dx.doi.org/10.2353/ajpath.2009.080924
   PubMed Web of Science ®Google Scholar
• Koo JS, Park S, Kim SI, Lee S, Park BW. The impact of caveolin protein expression in tumor stroma on prognosis of breast cancer. Tumour Biol 2011; 32:787 - 799; PMID: 21584795; http://dx.doi.org/10.1007/s13277-011-0181-6
   PubMed Web of Science ®Google Scholar
• Qian N, Ueno T, Kawaguchi-Sakita N, Kawashima M, Yoshida N, Mikami Y, et al. Prognostic significance of tumor/stromal caveolin-1 expression in breast cancer patients. Cancer Sci 2011; 102:1590 - 1596; PMID: 21585620; http://dx.doi.org/10.1111/j.13497006.2011.01985.x
   PubMed Web of Science ®Google Scholar
• Tanji K, Bonilla E. Light microscopic methods to visualize mitochondria on tissue sections. Methods 2008; 46:274 - 280; PMID: 18929660; http://dx.doi.org/10.1016/j.ymeth.2008.09.027
   PubMed Web of Science ®Google Scholar
• Mahad DJ, Ziabreva I, Campbell G, Laulund F, Murphy JL, Reeve AK, et al. Detection of cytochrome c oxidase activity and mitochondrial proteins in single cells. J Neurosci Methods 2009; 184:310 - 319; PMID: 19723540; http://dx.doi.org/10.1016/j.jneumeth.2009.08.020
   PubMed Web of Science ®Google Scholar
• Nachlas MM, Tsou KC, De Souza E, Cheng CS, Seligman AM. Cytochemical demonstration of succinic dehydrogenase by the use of a new p-nitrophenyl substituted ditetrazole. J Histochem Cytochem 1957; 5:420 - 436; PMID: 13463314; http://dx.doi.org/10.1177/5.4.420
   PubMed Web of Science ®Google Scholar
• Barrett T, Troup DB, Wilhite SE, Ledoux P, Rudnev D, Evangelista C, et al. NCBI GEO: mining tens of millions of expression profiles-database and tools update. Nucleic Acids Res 2007; 35:760 - 765; PMID: 17099226; http://dx.doi.org/10.1093/nar/gkl887
   PubMed Web of Science ®Google Scholar
• Brazma A, Parkinson H, Sarkans U, Shojatalab M, Vilo J, Abeygunawardena N, et al. ArrayExpress—a public repository for microarray gene expression data at the EBI. Nucleic Acids Res 2003; 31:68 - 71; PMID: 12519949; http://dx.doi.org/10.1093/nar/gkg091
   PubMed Web of Science ®Google Scholar
• Ertel A, Dean JL, Rui H, Liu C, Witkiewicz A, Knudsen KE, et al. RB-pathway disruption in breast cancer: Differential association with disease subtypes, disease-specific prognosis and therapeutic response. Cell Cycle 2010; 9:4153 - 4163; PMID: 20948315; http://dx.doi.org/10.4161/cc.9.20.13454
   PubMed Web of Science ®Google Scholar
• Camp RL, Dolled-Filhart M, Rimm DL. X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res 2004; 10:7252 - 7259; PMID: 15534099; http://dx.doi.org/10.1158/1078-0432.CCR-04-0713
   PubMed Web of Science ®Google Scholar